Moroz and colleagues showed the antitumor activity of radiolabeled antibodies directed against CDCP1 in preclinical models of pancreatic carcinoma (1). Pancreatic carcinoma is one of the most aggressive human cancers. Complete surgical resection followed by chemotherapy is the only available curative treatment, but concerns less than 20% of patients. Patients with inoperable or metastatic disease show median survival of 6 months. New systemic therapies are urgently needed, and Moroz and colleagues represent a promising new avenue of research. Radioligand therapies in oncology, which couple both imaging and cytotoxic treatment, have generated enthusiasm during the last decades (2). The CUB domain-containing protein 1 (CDCP1), a transmembrane protein highly overexpressed in human cancers, is an attractive target for cancer theranostics. Furthermore, CDCP1 contributes to pancreatic carcinoma progression through promotion of invasion, migration, and degradation of the extracellular matrix (3). However, CDCP1 expression has been little studied in the literature, and to our knowledge, the incidence of overexpression in pancreatic carcinoma and its independent prognostic value have never been assessed in large clinical series.
We retrospectively examined the normalized CDCP1 mRNA expression in 1,096 clinical pancreatic samples gathered from 16 public gene expression datasets (Supplementary Table S1), including 938 primary carcinomas and 158 normal tissues (4). CDCP1 was significantly overexpressed in cancers versus normal samples (P = 8.5E-27), and 58% of cancer samples showed overexpression according to a cut-off defined by 2-fold expression in normal samples. A total of 732 patients were informative for postoperative overall survival (OS). The median follow-up was 17 months (range, 1–156) after diagnosis, 511 patients died, and the 2-year OS was 39% [95% confidence interval (CI), 35–43] in the whole population. The 2-year OS was 34% (95% CI, 30–39) in the “CDCP1-high” group (N = 442) versus 46% (95% CI, 40–52) in the “CDCP1-low” group (N = 290; P = 3.48E-05, log-rank test). The HR for death was 1.47 (95% CI, 1.22–1.76) in the “CDCP1-high” group versus the “CDCP1-low” group (P = 3.88E-05, Wald test). In multivariate analysis including the variables significant in univariate analysis (American Joint Committee on Cancer stage and molecular subtypes), the CDCP1-based classification (P = 1.30E-03, Wald test) remained associated with OS, suggesting independent prognostic value. The same result was observed using CDCP1 expression as continuous variable.
Such a frequent overexpression of CDCP1 in pancreatic carcinoma and its independent prognostic value in this large series, the largest one reported to date to our knowledge, nicely complement the Moroz and colleagues’ results and further support the development of CDCP1-targeting radiolabeled therapies in this so devastating disease.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.